Diabetic peripheral neuropathy: Molecular staging, risk factors, therapeutics, and emerging trends
image: Figure 7 summarizes the integrated framework proposed in this review. Diabetic peripheral neuropathy is organized into three progressive pathogenic stages: metabolic dysregulation, chronic inflammation, and overt neuronal damage. Within this framework, six representative subtypes are mapped onto the three stages, while redox disequilibrium is highlighted as a central mechanistic hub linking subtype heterogeneity to disease progression. The figure also illustrates cold atmospheric plasma as an emerging redox-modulating intervention with potential relevance to metabolic reprogramming, inflammation attenuation, and neurogenesis promotion.
Credit: Xiaofeng Dai
Diabetic peripheral neuropathy (DPN) is one of the most common and disabling complications of diabetes, yet its clinical manifestations and pathogenic drivers are highly heterogeneous. This heterogeneity makes it difficult to build a unified mechanistic understanding and to develop precise, subtype-specific therapeutic strategies.
In this review, Dai and Tang organize DPN into an integrated three-stage framework consisting of metabolic dysregulation, chronic inflammation, and overt neuronal damage. Six representative subtypes—hyperglycemia-driven DPN, dyslipidemia-driven DPN, inflammation-driven DPN, dysvascularity-driven DPN, small-fiber DPN, and large-fiber DPN—are mapped onto these stages. The review identifies redox disequilibrium as a central mechanism linking metabolic injury, inflammatory amplification, vascular dysfunction, and neuronal damage.
The review also summarizes major risk factors across genetic, epigenetic, and phenotypic/metabolic levels, with emphasis on metabolic drivers as upstream initiators of neuroinflammatory and neurodegenerative cascades. Current therapeutic strategies are evaluated according to their alignment with different pathogenic stages, including metabolic regulation, anti-inflammatory approaches, and nerve repair.
In addition, the review discusses cold atmospheric plasma (CAP) as an emerging multimodal, redox-modulating intervention with potential cross-stage relevance. The authors emphasize that CAP remains an investigational direction for DPN and that further mechanistic studies, preclinical validation, and clinical trials are needed to clarify its safety, dosing window, and therapeutic value.
Overall, this review provides a unified staging model for DPN that may support future development of stage-specific biomarkers, patient stratification strategies, and more precise therapeutic approaches.
(Expert Contact: if applicable)
Xiaofeng Dai
The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University
Email: xiaofengteam@163.com
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New Med Research review maps diabetic peripheral neuropathy into a three-stage, six-subtype framework and discusses CAP as an emerging redox-modulating strategy.